Biomedical subjects

Petros Koumoutsakos

Publications and source records attributed to Petros Koumoutsakos.

11 recordsLinked to original sources

PubMed2006

R-leaping: accelerating the stochastic simulation algorithm by reaction leaps.

A novel algorithm is proposed for the acceleration of the exact stochastic simulation algorithm by a predefined number of reaction firings (R-leaping) that may occur across several reaction channels. In the present approach, the numbers of reaction firings are correlated binomial distributions and the sampling procedure is independent of any permutation of the reaction channels. This enables the algorithm to efficiently handle large systems with disparate rates, providing substantial computational savings in certain cases. Several mechanisms for controlling the accuracy and the appearance of negative species are described. The advantages and drawbacks of R-leaping are assessed by simulations on a number of benchmark problems and the results are discussed in comparison with established methods.

Journal Article↗

PubMed2006

Nanoparticle traffic on helical tracks: thermophoretic mass transport through carbon nanotubes.

Using molecular dynamics simulations, we demonstrate and quantify thermophoretic motion of solid gold nanoparticles inside carbon nanotubes subject to wall temperature gradients ranging from 0.4 to 25 K/nm. For temperature gradients below 1 K/nm, we find that the particles move "on tracks" in a predictable fashion as they follow unique helical orbits depending on the geometry of the carbon nanotubes. These findings markedly advance our knowledge of mass transport mechanisms relevant to nanoscale applications.

Computer Simulation↗

PubMed2006

Simulations of optimized anguilliform swimming.

The hydrodynamics of anguilliform swimming motions was investigated using three-dimensional simulations of the fluid flow past a self-propelled body. The motion of the body is not specified a priori, but is instead obtained through an evolutionary algorithm used to optimize the swimming efficiency and the burst swimming speed. The results of the present simulations support the hypothesis that anguilliform swimmers modify their kinematics according to different objectives and provide a quantitative analysis of the swimming motion and the forces experienced by the body. The kinematics of burst swimming is characterized by the large amplitude of the tail undulations while the anterior part of the body remains straight. In contrast, during efficient swimming behavior significant lateral undulation occurs along the entire length of the body. In turn, during burst swimming, the majority of the thrust is generated at the tail, whereas in the efficient swimming mode, in addition to the tail, the middle of the body contributes significantly to the thrust. The burst swimming velocity is 42% higher and the propulsive efficiency is 15% lower than the respective values during efficient swimming. The wake, for both swimming modes, consists largely of a double row of vortex rings with an axis aligned with the swimming direction. The vortex rings are responsible for producing lateral jets of fluid, which has been documented in prior experimental studies. We note that the primary wake vortices are qualitatively similar in both swimming modes except that the wake vortex rings are stronger and relatively more elongated in the fast swimming mode. The present results provide quantitative information of three-dimensional fluid-body interactions that may complement related experimental studies. In addition they enable a detailed quantitative analysis, which may be difficult to obtain experimentally, of the different swimming modes linking the kinematics of the motion with the forces acting on the self-propelled body. Finally, the optimization procedure helps to identify, in a systematic fashion, links between swimming motion and biological function.

Animals↗

PubMed2005

Simulations of (an)isotropic diffusion on curved biological surfaces.

We present a computational particle method for the simulation of isotropic and anisotropic diffusion on curved biological surfaces that have been reconstructed from image data. The method is capable of handling surfaces of high curvature and complex shape, which are often encountered in biology. The method is validated on simple benchmark problems and is shown to be second-order accurate in space and time and of high parallel efficiency. It is applied to simulations of diffusion on the membrane of endoplasmic reticula (ER) in live cells. Diffusion simulations are conducted on geometries reconstructed from real ER samples and are compared to fluorescence recovery after photobleaching experiments in the same ER samples using the transmembrane protein tsO45-VSV-G, C-terminally tagged with green fluorescent protein. Such comparisons allow derivation of geometry-corrected molecular diffusion constants for membrane components from fluorescence recovery after photobleaching data. The results of the simulations indicate that the diffusion behavior of molecules in the ER membrane differs significantly from the volumetric diffusion of soluble molecules in the lumen of the same ER. The apparent speed of recovery differs by a factor of approximately 4, even when the molecular diffusion constants of the two molecules are identical. In addition, the specific shape of the membrane affects the recovery half-time, which is found to vary by a factor of approximately 2 in different ER samples.

Animals↗

PubMed2005

Single-particle tracking of murine polyoma virus-like particles on live cells and artificial membranes.

The lateral mobility of individual murine polyoma virus-like particles (VLPs) bound to live cells and artificial lipid bilayers was studied by single fluorescent particle tracking using total internal reflection fluorescence microscopy. The particle trajectories were analyzed in terms of diffusion rates and modes of motion as described by the moment scaling spectrum. Although VLPs bound to their ganglioside receptor in lipid bilayers exhibited only free diffusion, analysis of trajectories on live 3T6 mouse fibroblasts revealed three distinct modes of mobility: rapid random motion, confined movement in small zones (30-60 nm in diameter), and confined movement in zones with a slow drift. After binding to the cell surface, particles typically underwent free diffusion for 5-10 s, and then they were confined in an actin filament-dependent manner without involvement of clathrin-coated pits or caveolae. Depletion of cholesterol dramatically reduced mobility of VLPs independently of actin, whereas inhibition of tyrosine kinases had no effect on confinement. The results suggested that clustering of ganglioside molecules by the multivalent VLPs induced transmembrane coupling that led to confinement of the virus/receptor complex by cortical actin filaments.

Actins↗

PubMed2005

Effects of organelle shape on fluorescence recovery after photobleaching.

The determination of diffusion coefficients from fluorescence recovery data is often complicated by geometric constraints imposed by the complex shapes of intracellular compartments. To address this issue, diffusion of proteins in the lumen of the endoplasmic reticulum (ER) is studied using cell biological and computational methods. Fluorescence recovery after photobleaching (FRAP) experiments are performed in tissue culture cells expressing GFP-KDEL, a soluble, fluorescent protein, in the ER lumen. The three-dimensional (3D) shape of the ER is determined by confocal microscopy and computationally reconstructed. Within these ER geometries diffusion of solutes is simulated using the method of particle strength exchange. The simulations are compared to experimental FRAP curves of GFP-KDEL in the same ER region. Comparisons of simulations in the 3D ER shapes to simulations in open 3D space show that the constraints imposed by the spatial confinement result in two- to fourfold underestimation of the molecular diffusion constant in the ER if the geometry is not taken into account. Using the same molecular diffusion constant in different simulations, the observed speed of fluorescence recovery varies by a factor of 2.5, depending on the particular ER geometry and the location of the bleached area. Organelle shape considerably influences diffusive transport and must be taken into account when relating experimental photobleaching data to molecular diffusion coefficients. This novel methodology combines experimental FRAP curves with high accuracy computer simulations of diffusion in the same ER geometry to determine the molecular diffusion constant of the solute in the particular ER lumen.

Animals↗

PubMed2005

Curvature induced L-defects in water conduction in carbon nanotubes.

We conduct molecular dynamics simulations to study the effect of the curvature induced static dipole moment of small open-ended single-walled carbon nanotubes (CNTs) immersed in water. This dipole moment generates a nonuniform electric field, changing the energy landscape in the CNT and altering the water conduction process. The CNT remains practically filled with water at all times, whereas intermittent filling is observed when the dipole term is not included. In addition, the dipole moment induces a preferential orientation of the water molecules near the end regions of the nanotube, which in turn causes a reorientation of the water chain in the middle of the nanotube. The most prominent feature of this reorientation is an L-defect in the chain of water molecules inside the CNT. The analysis of the water energetics and structural characteristics inside and in the vicinity of the CNT helps to identify the role of the dipole moment and to suggest possible mechanisms for controlled water and proton transport at the nanoscale.

Computer Simulation↗

PubMed2004

Dispersion corrections to density functionals for water aromatic interactions.

We investigate recently published methods for extending density functional theory to the description of long-range dispersive interactions. In all schemes an empirical correction consisting of a C6r(-6) term is introduced that is damped at short range. The coefficient C6 is calculated either from average molecular or atomic polarizabilities. We calculate geometry-dependent interaction energy profiles for the water benzene cluster and compare the results with second-order Møller-Plesset calculations. Our results indicate that the use of the B3LYP functional in combination with an appropriate mixing rule and damping function is recommended for the interaction of water with aromatics.

Journal Article↗

PubMed2004

Self-organizing nets for optimization.

Given some optimization problem and a series of typically expensive trials of solution candidates sampled from a search space, how can we efficiently select the next candidate? We address this fundamental problem by embedding simple optimization strategies in learning algorithms inspired by Kohonen's self-organizing maps and neural gas networks. Our adaptive nets or grids are used to identify and exploit search space regions that maximize the probability of generating points closer to the optima. Net nodes are attracted by candidates that lead to improved evaluations, thus, quickly biasing the active data selection process toward promising regions, without loss of ability to escape from local optima. On standard benchmark functions, our techniques perform more reliably than the widely used covariance matrix adaptation evolution strategy. The proposed algorithm is also applied to the problem of drag reduction in a flow past an actively controlled circular cylinder, leading to unprecedented drag reduction.

Neural Networks, Computer↗

PubMed2004

Remeshed smoothed particle hydrodynamics simulation of the mechanical behavior of human organs.

In computer aided surgery the accurate simulation of the mechanical behavior of human organs is essential for the development of surgical simulators. In this paper we introduce particle based simulations of two different human organ materials modeled as linear viscoelastic solids. The constitutive equations for the material behavior are discretized using a particle approach based on the Smoothed Particle Hydrodynamics (SPH) method while the body surface is tracked using level sets. A key aspect of this approach is its flexibility which allows the simulation of complex time varying topologies with large deformations. The accuracy of the original formulation is significantly enhanced by using a particle reinitialization technique resulting in remeshed Smoothed Particle Hydrodynamics (rSPH). The mechanical parameters of the systems used in the simulations are derived from experimental measurements on human cadaver organs. We compare the mechanical behavior of liver- and kidney-like materials based on the dynamic simulations of a tensile test case. Moreover, we present a particle based reconstruction of the liver topology and its strain distribution under a small local load. Finally, we demonstrate a unified formulation of fluid structure interaction based on particle methods.

Biomechanical Phenomena↗

PubMed2003

Reducing the time complexity of the derandomized evolution strategy with covariance matrix adaptation (CMA-ES).

This paper presents a novel evolutionary optimization strategy based on the derandomized evolution strategy with covariance matrix adaptation (CMA-ES). This new approach is intended to reduce the number of generations required for convergence to the optimum. Reducing the number of generations, i.e., the time complexity of the algorithm, is important if a large population size is desired: (1) to reduce the effect of noise; (2) to improve global search properties; and (3) to implement the algorithm on (highly) parallel machines. Our method results in a highly parallel algorithm which scales favorably with large numbers of processors. This is accomplished by efficiently incorporating the available information from a large population, thus significantly reducing the number of generations needed to adapt the covariance matrix. The original version of the CMA-ES was designed to reliably adapt the covariance matrix in small populations but it cannot exploit large populations efficiently. Our modifications scale up the efficiency to population sizes of up to 10n, where n is the problem dimension. This method has been applied to a large number of test problems, demonstrating that in many cases the CMA-ES can be advanced from quadratic to linear time complexity.

Algorithms↗